Safety Evaluation of a Q-fever Vaccine, NDBR 105: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Evaluation of a Q-fever Vaccine, NDBR 105 (NCT00584454), a na phase 2 study. The primary outcome is The Adverse Reaction and Occupational Illness Endpoint Measurements in This Q Fever NDBR 105 Vaccine Study Will be Evaluated for All Intent-to-treat Volunteers..

2. Clinical Question

This is principally a safety and occupational-illness monitoring question, rather than a comparative efficacy question. The registry’s study purpose is to evaluate vaccine safety and collect data on the incidence of occupational Q fever infection among personnel at risk. The posted record does not give an estimate of vaccine effectiveness or a comparison of illness rates between groups. Without a separate comparator, the observed counts can describe what the registry records for this study group, but they cannot establish how those outcomes would compare under a different intervention or without vaccination.

3. Trial Design

The registry identifies this study as Phase 2 and single-group. Its title describes a continued safety evaluation of Q Fever Vaccine NDBR 105 in people at risk of exposure to Coxiella burnetii. The study is listed as completed, with enrollment of 10. The recorded start is 2006-02, and primary completion is recorded as 2009-07. The sponsor is the U.S. Army Medical Research and Development Command.

Allocation is listed as NA, and masking as none. There is no separate control arm in the record. Consequently, the data are not from a randomized comparison, and the vaccine-group summaries should not be read as if they were contrasted with a comparable control group. A single-group safety record can document reported events in the enrolled group, but it cannot by itself separate events associated with vaccination from events that could occur in the population for other reasons.

The intervention is listed as a biological intervention named Q Fever Vaccine NDBR 105. The arm description says volunteers will receive an intradermal dose of 0.1 ml of skin test antigen in the volar aspect of the arm, followed by evaluation of the skin test. It says erythema after the skin test medically contraindicates vaccination, but the registry text ends mid-sentence. The complete procedure for determining who proceeded to vaccination is not reported in the registry record.

The endpoint title refers to all intent-to-treat volunteers. The record does not explain how that analysis population was defined in practice, how many volunteers received vaccine, or whether any participants were excluded from outcome summaries. It also lists no analysis entries. Thus, the design information establishes the broad single-group safety framework, but it does not provide a detailed account of the analysis procedures or participant flow.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Patients were excluded from this study if after the skin test antigen erythema (\> 30mm) or induration (\> 20 mm) occured

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects at risk of exposure to Coxiella Burnetti (Q Fever)

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as The Adverse Reaction and Occupational Illness Endpoint Measurements in This Q Fever NDBR 105 Vaccine Study Will be Evaluated for All Intent-to-treat Volunteers., measured over AEs recorded through day 28 after vaccination; SAEs recorded through duration of study; Confirmed occupational illness recorded through duration of study.

The primary endpoint is described as adverse-reaction and occupational-illness endpoint measurements among all intent-to-treat volunteers. Its unit is participants, and its parameter is a count of participants. In plain terms, the endpoint is intended to record how many participants experienced the specified outcomes, rather than to report a continuous measurement such as a laboratory value.

The registry identifies several observation periods. Adverse events are recorded through day 28 after vaccination. Serious adverse events and confirmed occupational illness are recorded through the duration of the study. The endpoint description also refers to 7 days of follow-up after receipt of skin test antigen and 12 months of follow-up after receipt of vaccine. These descriptions indicate that the safety and occupational-illness outcomes do not all have the same stated observation window.

Counting participants with events is a useful way to describe the frequency of recorded outcomes in a safety study. It provides a direct account of how many people had an event under the registry’s definitions. The count alone does not describe how severe an event was, when it began, how long it lasted, or whether it was judged to be caused by the intervention. Those details require additional outcome definitions and participant-level or event-level reporting.

Although the record lists one outcome measure, it does not include numerical results for the primary endpoint or define the criteria used to classify an adverse reaction or occupational illness. Those details are not reported in the registry record. The endpoint can therefore be described from its stated purpose and timing, but its event counts and full operational definition cannot be reconstructed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary outcome, each participant is classified according to whether the event occurred under the study’s definition. A count of participants with an event is a direct summary of such an outcome. In this study, the primary measure is specified in participant counts. The registry does not report the primary outcome counts, so the stated endpoint cannot be independently assessed from the posted entry.

What does a participant count describe?

A participant count describes the number recorded as having an outcome in the defined group and observation period. It is not the same as a count of all event episodes: one person may experience more than one event, and a record may report participants, events, or both. Here, the primary endpoint specifies participants as the unit. The adverse-event summary separately reports affected-participant fields and event terms. The record does not explain how recurrent events or participants with multiple terms were handled.

Interpretation also depends on the denominator and follow-up. A proportion is meaningful only when its numerator, denominator, population, and observation period are understood. The registry’s adverse summary includes at-risk and affected counts, while the primary endpoint description gives more than one follow-up window. The record does not provide enough detail to align every adverse-event summary with a specific endpoint definition and observation period. No additional proportion should be inferred from those fields.

Why does the study design matter?

In a randomized comparison, allocation can support a direct comparison between groups, subject to the study’s conduct and analysis. This registry lists a single-group model, allocation as NA, and no masking. There is no like-for-like control group in the posted design. Thus, the observed event summaries describe the study group, but they do not estimate a difference attributable to the vaccine. General statistical interpretation of an event count does not overcome the absence of a comparator.

Single-group safety studies can still be informative as descriptions of reported events under the study’s follow-up procedures. Their interpretation depends on consistent event definitions, complete follow-up, and transparent reporting of who received the intervention and who contributed data. The registry record does not give a participant-flow account or say how the intent-to-treat population was implemented. It also does not report the number vaccinated or details on outcome ascertainment beyond the stated windows.

How should uncertainty be considered?

Statistical uncertainty reflects the fact that the recorded study group is not necessarily a precise guide to outcomes in a broader population. In general, a confidence interval gives a range of values compatible with the data and a specified statistical method. The registry does not report confidence intervals for the event summaries, and no analysis entries are listed. Therefore, the precision of the posted counts and term percentages cannot be evaluated using interval estimates from this record.

Small groups often yield imprecise estimates, particularly for uncommon events. This is a general statistical consideration, not a numerical estimate for this trial. A count of zero, if one were reported, would not by itself prove that an event cannot occur; similarly, an observed event count does not establish causation. The registry does not provide a numerical primary outcome result, so no event-rate estimate or interval can be reconstructed.

What do the planning assumptions mean?

The registry includes a planning note describing an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and that time-to-event calculations use total events while other calculations use participants per arm. This is a general planning framework, not a description of the actual single-group design. The note does not establish that the trial used these assumptions to choose enrollment, and no numerical planning estimates are reported in the registry record.

Planning calculations describe what a hypothetical study might require under specified assumptions. They are not observed power and do not demonstrate that a completed study was sufficiently informative. They also cannot be used as evidence of an effect when outcome estimates and a comparison are not available. Any planning illustration should be interpreted separately from the enrolled study’s design and posted safety summaries.

Why can event categories be difficult to interpret?

Adverse-event summaries depend on how terms are coded, grouped, and judged. Seriousness is a classification, while severity describes intensity; the two concepts are not interchangeable. The record lists serious terms but does not provide definitions or explain how seriousness and attribution were assessed. The appearance of a term in a serious-event summary should therefore be reported as a registry classification, not treated as an independent causal conclusion.

More generally, over-dispersion matters when observed variability exceeds what a simple statistical model assumes. It can affect standard errors and the reliability of some model-based intervals or tests. The registry record does not report an over-dispersion analysis or a model for the outcomes. Because the endpoint is described as participant counts and the analysis entries are absent, a model-based interpretation cannot be specified from this record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Q Fever Vaccine (NDBR 105)")
n      <- c(10)
events <- c(10)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Q Fever Vaccine (NDBR 105)  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analysis entries. It does not report a statistical analysis plan, the hierarchy of outcomes, or whether any adjustment for multiple testing was planned or used. Multiplicity refers generally to the increased chance of at least one false-positive finding when many statistical hypotheses are tested. Whether that issue applies, and how it might have been handled, cannot be determined from the registry record.

Although a single outcome measure is listed, the study purpose and endpoint description encompass adverse reactions and occupational illness, and the adverse summary includes several event terms. The record does not explain whether these were treated as separate formal hypotheses, descriptive safety summaries, or components of a prespecified analysis. It would be inappropriate to assume a multiplicity procedure or to infer that none was needed.

Missing-data handling is not reported in the registry record. There is no account of losses to follow-up, incomplete outcome assessments, or how unavailable observations were treated. The listed enrollment does not establish that every enrolled participant contributed data at every follow-up window. The record also does not state how participants who did not proceed from skin testing to vaccination, if any, were handled in the analysis.

The primary endpoint title refers to all intent-to-treat volunteers, but the registry does not define the analysis population or provide participant flow. It does not report whether the adverse-event summaries use that same population. These omissions limit the ability to judge whether the reported safety categories and the planned endpoint refer to the same set of participants or observation periods. No assumptions about exclusions, missingness, or analysis population can be made from the available record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chills (10.0%), paraesthesia (10.0%), malaise (10.0%).

The registry’s adverse-event summary lists one vaccine group. It records 10 at risk and 1 affected for the serious-event category, and 10 at risk and 10 affected for the other-event category. The top serious terms are Chills, Paraesthesia, and Malaise, each listed at 10.0%. These are the figures and labels posted in the registry record; they should not be treated as a comparison between treatment groups.

Seriousness and severity are different concepts. Seriousness is generally a regulatory or clinical classification based on specified consequences, whereas severity describes the intensity of an event. The registry does not report the definitions or assessment process used for these terms. It also does not state whether a listed term was considered related to vaccination. The term listing alone cannot establish causation, severity, duration, or outcome.

The death field is null, so deaths are not reported in the registry record. A null field should not be read as a confirmed count of zero. The record also does not provide event narratives, timing, recurrence information, or detail about how term-level percentages were calculated. These limitations make the adverse-event summary a narrow description rather than a complete safety account.

13. What the Result Does, and Does Not, Mean

The record describes a Phase 2 safety evaluation of Q Fever Vaccine NDBR 105 in a group of people at risk of Q fever exposure. It states that the study was completed and records enrollment of 10. The posted adverse-event summary provides group-level affected counts and several serious-event terms. Those data can be read as descriptive information about the entries recorded for this study.

The record does not provide numerical results for the stated primary endpoint, a confirmed occupational illness count, or analysis entries. It does not report confidence intervals or a statistical analysis plan. Consequently, the precision of the primary endpoint and the strength of any statistical evidence cannot be assessed from the posted record. The adverse-event counts and term percentages do not replace the missing primary outcome results.

The study has no separate comparator group. Its design therefore cannot estimate how the recorded events would differ from outcomes in a comparable group not receiving the vaccine or receiving another intervention. Observing an event after an intervention does not, by itself, demonstrate that the intervention caused it. Likewise, the absence of a reported event cannot establish that the event is impossible.

The record’s purpose includes collecting information about occupational Q fever infection, but the registry entry does not report a numerical result for confirmed occupational illness. It therefore cannot support a conclusion about the incidence of occupational infection in this study group. The stated follow-up windows provide context for what was intended to be monitored, not a substitute for reported outcome data.

Overall, the posted information supports a limited description of the study design and adverse-event fields. It does not establish comparative safety, vaccine effectiveness, or a causal effect on occupational illness. Important details about outcome definitions, participant flow, missing data, and analysis methods are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it highlights the distinction between descriptive safety monitoring and comparative evidence. A single-group study can record adverse events and occupational illness in a defined population, but without a control group it cannot estimate a between-group difference. The record explicitly identifies a single-group design and no masking, so its adverse-event summaries should be interpreted as descriptive rather than comparative.

The endpoint also illustrates why outcome definitions and follow-up periods matter. The registry refers to adverse events through day 28 after vaccination, serious adverse events through the duration of the study, and confirmed occupational illness through the duration of the study. Its endpoint description separately notes follow-up after skin test antigen and after vaccination. Different windows can capture different outcomes, and careful interpretation requires knowing which observations belong to each defined period.

Another statistical lesson is the difference between a listed count and a complete analysis. The record supplies adverse-event summary fields but no numerical result for its primary endpoint and no analysis entries. Counts can be informative, yet without clear denominators, outcome definitions, participant flow, and uncertainty estimates, they do not provide a full account of the endpoint or its precision.

Finally, the planning note describes hypothetical two-arm calculations, while the registered study is single-group. Keeping planning illustrations separate from the actual design prevents them from being mistaken for observed evidence or a justification for the enrollment. The record does not report whether those assumptions informed the trial’s design. The case underscores the value of transparent reporting of analysis plans, missing data, and outcome results alongside safety summaries.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record contains limited detail about how the study was conducted and analyzed. The arm description is incomplete: it describes skin testing and a medical contraindication to vaccination after erythema, but ends mid-sentence. The record does not explain how this condition affected enrollment, who proceeded to vaccination, or how any such participants were handled analytically.

Although the endpoint title refers to all intent-to-treat volunteers, the record does not define that population or provide participant flow. It does not report how many participants received vaccine, whether all enrolled participants completed follow-up, or how incomplete observations were treated. The endpoint’s stated follow-up descriptions include multiple periods, but the record does not clarify how the adverse-event summaries map to those periods.

Outcome reporting is also incomplete. The registry lists one primary outcome measure but no numerical primary result and no analysis entries. It does not provide a numerical count for confirmed occupational illness, detailed event definitions, event narratives, or the process for judging seriousness and attribution. The death field is null, and deaths are not reported in the registry record.

The single-group design does not include a randomized comparator. This limits causal interpretation and prevents a like-for-like estimate of relative safety. The record also does not report a statistical analysis plan, missing-data methods, confidence intervals, or interim-analysis details. The planning note’s hypothetical two-arm assumptions do not fill these gaps or establish the study’s actual design justification.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety Evaluation of a Q-fever Vaccine, NDBR 105 — NCT00584454.
• Registry record last updated 2020-01-03; status last verified 2019-12.
• Results first posted 2017-03-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry identifies NCT00584454 as a completed Phase 2, single-group safety study of Q Fever Vaccine NDBR 105 in people at risk of exposure to Coxiella burnetii. Enrollment is 10. The recorded start is 2006-02, and primary completion is 2009-07. Allocation is NA, and masking is none.

The primary endpoint is described as counts of participants with adverse reactions and occupational illness. The registry states that adverse events were recorded through day 28 after vaccination, while serious adverse events and confirmed occupational illness were recorded through the duration of the study. The adverse-event summary lists one group, including serious-event fields and three top serious terms at 10.0% each.

Numerical primary endpoint results, analysis entries, a comparator group, and details of the statistical analysis are not reported in the registry record. The posted adverse-event information is descriptive and does not establish causation or comparative safety.